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Scientific collaboration between GIBH and CRG: 2 Postdoctoral Positions to study stem cell physiology and somatic cell reprogramming at the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China

Ilda showed that the Paternally Expressed Gene-3 (PEG 3) is a novel regulator of somatic cell reprogramming. Peg 3 enhances cell reprogramming by acting on cell metabolism.

Theka et al. Scientific Reports 2017 Aug 29;7(1):9705.

https://www.nature.com/articles/s41598-017-10016-7

 

Retinitis pigmentosa covers a group of rare genetic disorders that cause retinal degeneration due to a loss of photoreceptors, the specialized cell-sensitive neurons that enable eyesight. By transplanting Wnt-activated hematopoietic stem and progenitor cells (HSPCs) we demonstrated that Muller cells can be reprogrammed in vivo after fusion with HSPCs. The newly generated hybrids can differentiate in photoreceptors leading to partial retina regeneration and to a certain degree of functional rescue. Sanges D, Simonte G DiVicino U, Romo N, Pinilla I, Nicolás Farrés M and Cosma MP (2016). In vivo conversion of Müller glia into photoreceptors through cell fusion-mediated reprogramming. Journal of Clinical Investigation, Aug 1;126(8):3104-3116

Our paper on Parkinson’s disease therapy is in press in EBioMedicine (http://www.ebiomedicine.com/article/S2352-3964(16)30151-7/abstract), a new online journal supported by Cell press and Lancet.  A definitive therapy for Parkinson’s disease is not available. In this work, we transplanted hematopoietic stem and progenitor cells into the substantia nigra of brains of two different mouse models of Parkinson’s disease. These transplanted cells fused with neurons and glial cells of the recipient mice. Four weeks after transplantation, the hybrids acquired features of mature astroglia, secreted Wnt1, and functionally ameliorated dopaminergic neuron loss. Current cell therapy approaches are being pursued in the striatum with the aim to increase dopamine levels. Here we show that the loss of dopaminergic neurons can be protected against by direct actions in the substantia nigra.

Altarche-Xifro W, Di Vicino U, Muñoz-Martin MI, Bové J, Vila M and Cosma MP (2016). Functional rescue of dopaminergic neuron loss in Parkinson’s disease mice after transplantation of hematopoietic stem and progenitor cells, EBioMedicine, in press. 

In March 2016 I was honored to receive the “Ciutat de Barcelona” award 2015 in Life Science for our work carried out in collaboration with Melike Lakadamyali group. The ceremony took place at the “Saló de Cent de l’Ajuntament de Barcelona”. The event can be seen at : BTV: http://www.btv.cat/alacarta/btv-directe/43673/

Pictures by ©pepherrero

 

 

 

 

the Awardees…

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With Ada Colau, the mayor of Barcelona….

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With Maria Aurelia Ricci, the first author of our work published in Cell 2015….

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Our work published in Cell last year ( Ricci MA, Manzo C, García-Parajo M, *Lakadamyali M, and *Cosma MP (2015). Chromatin fibers are formed by heterogeneous groups of nucleosomes in vivo. Cell, *co-last authors. Nominated F1000Prime 2015) has been selected to be among the best 8 research in Spain. In collaboration with the group of Melike Lakadamyali using super resolution microscopy we dissected out the nanoscale organisation of the nucleosome assembly in a variety of somatic and stem/ reprogrammed cells. We discovered that nucleosomes are arranged into discrete groups, which we called ‘nucleosome clutches’ (in analogy with egg clutches) and not in a regular hierarchical structure, as it was believed for a long time and is reported in textbooks. Nucleosome median number and clutch compaction correlate closely with cellular state.

Picture by David Airob, La Vanguardia

 

Hello everybody!

Wednesday, 23 March 2016 by

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We have shown that cyclic activation of the Wnt/b-catenin signalling pathway enhances cell-fusion-mediated reprogramming of a variety of somatic cells (Lluis et al., Cell Stem Cell 2008, Marucci et al. Cell Reports 2014). Tcf3 and Tcf1 are two key effectors in the pathway, and are essential in this process (Lluis et al., PNAS 2011; Ombrato et al., Cell Cycle 2012; Aulicino et al., Stem Cell Report 2014).

Currently we are studying how the dynamics of the Wnt pathway maintains cell pluripotency, and we are reconstructing the regulatory network that is controlled by b-catenin/Tcf factors that have pivotal roles in the regulation of pluripotency in embryonic stem cells and somatic cell reprogramming.

Using super-resolution fluorescence microscopy (stochastic optical reconstruction microscopy; STORM) (Rust et al., Nature Methods, 2006) in collaboration with the group of Melike Lakadamyali (Institute of Photonic Sciences, Barcelona) we have dissected out the nanoscale organization of nucleosome assembly, with high molecular specificity and spatial resolution in a variety of somatic and stem/ reprogrammed cells. We discovered that nucleosomes are arranged into discrete groups, which we called ‘nucleosome clutches’ (as an analogy with egg clutches). While somatic cells have dense and compacted clutches that contain tens of nucleosomes, clutches in pluripotent cells contain fewer and less compacted nucleosomes. Our findings have delineated a novel model of chromatin fiber assembly, and the relationship among the decoded structure and naïve pluripotency (Ricci et al. Cell 2015).

We are currently studying the changes in chromatin structure and organisation during somatic cell reprogramming and differentiation, to determine how chromatin fibers can be rearranged to overcome epigenetic barriers to gain pluripotency.

We have shown that upon activation of Wnt/b-catenin signalling, mouse retinal neurons can be transiently reprogrammed in vivo. These cells return to a precursor stage following their spontaneous fusion with transplanted haematopoietic stem and progenitor cells in damaged retinas. The newly formed hybrid cells reactivate neuronal precursor genes, and can thereby proliferate. The hybrids differentiate into neurons, which regenerate the damaged retinal tissue to provide functional rescue. Our data suggest that in-vivo reprogramming of terminally differentiated retinal neurons is a mechanism of tissue regeneration (Sanges et al., Cell Reports 2013).

We recently described retinal regeneration in rd10 mice, which is a model of retinitis pigmentosa, a severe disease that affects a large number of individuals and that results in progressive loss of vision (Sanges et al JCI 2010). Furthermore, we demonstrated cell-fusion mediated reprogramming as an efficient therapy for Parkinson’s disease, and as mechanism to control liver regeneration, an organ with high regenerative capacity in mammals (Altarche-Xifro et al eBiomedicine 2016; Pedone et al. Cell Reports 2017). We are also investigating the mechanisms controlling cell-to-cell fusion, and how ploidy is controlled in reprogrammed hybrids.

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